Triple quadrupole mass spectrometers are used widely for the analysis of a variety of substances. As the name denotes, triple quadrupole mass spectrometers include three quadrupole structures for mass analysis: a first quadrupole (also referred to as a quadrupole mass filter, or QMF) that selectively transmits precursor ions having a specified mass-to-charge ratio (m/z), a second quadrupole positioned within a gas-filled enclosure (referred to as a collision cell) for receiving the precursor ions transmitted through the first resolving quadrupole and causing the ions to undergo fragmentation into product ions, and a third quadrupole that receives the product ions from the second quadrupole and selectively transmits product ions having a specified m/z to a detector. The first, second and third quadrupoles are referred to herein as Q1, Q2 and Q3, respectively.
Selective reaction monitoring (SRM) is commonly employed in triple quadrupole mass spectrometers to detect and quantify targeted analytes. In SRM, Q1 and Q3 (both of which are operated as QMFs) are tuned to respectively transmit only the characteristic precursor and product ions of the targeted analyte. The monitored m/z values of the precursor and product ions are called a transition. By selecting the appropriate transition, an analyte may be detected and/or quantified at high sensitivity and with high specificity. When concurrent measurement of multiple analytes is desired, the Q1 and Q3 are operated to rapidly cycle between different transitions, each corresponding to one of the targeted analytes. This mode of operation is referred to as multiple reaction monitoring (MRM).
A key performance metric of modern triple quadrupole mass spectrometers is the rate at which MRM analysis may be conducted, i.e., the number of transitions that may be cycled through per unit time. Some commercial manufacturers advertise their instruments as being capable of monitoring in excess of 500 transitions/second. High MRM rates are facilitated by accelerating the transmission of ions through the relatively high-pressure environment of the collision cell (Q2) by establishing an axial direct current (DC) field that urges ions toward the exit of Q2. The axial DC field, sometimes called a “drag field”, is typically established by applying potentials to a set of auxiliary electrodes (drag vanes) positioned between the rod electrodes that constitute the quadrupole. Electrode structures and associated methods for creating a drag field are disclosed, for example, in U.S. Pat. No. 7,675,031 (“Auxiliary Drag Field Electrodes” by Konicek et al., issued Mar. 9, 2010), the disclosure of which is incorporated herein by reference.
It is known that the phenomenon of cross-talk may significantly compromise performance when a triple quadrupole mass spectrometer is operated at high MRM rates. Cross-talk occurs when there are two consecutive transitions with the same m/z product ions generated from precursor ions of different m/z's. Due to the high MRM rate, the collision cell (Q2) may not have sufficient time to clear the product ions from the first transition before switching to the second transition. In these cases product ions from earlier transitions can appear in the chromatogram for the second transition as a “ghost peak”. The cross-talk effect can be particularly problematic if the ions corresponding to the first transition are of high intensity, as it can lead to more plausible false positives on the subsequent transition.
It is an objective of the present invention to provide a method of operating a triple quadrupole mass spectrometer, and in particular the collision cell thereof, to avoid or minimize cross-talk at high MRM rates while still maintaining good sensitivity.